Biopharmaceutical evaluation of ophthalmic excipients using in vitro and ex vivo corneal models
| Autor: | Juretić, Marina |
|---|---|
| Přispěvatelé: | Pepić, Ivan |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
eye-related bioavailability
nanosustavi površinski aktivni ekscipijensi Pharmacology. Therapeutics. Toxicology ophthalmic drugs oftalmički lijek HCE-T nanosystems surfactants ophthalmic drugs ophthalmic excipients surfactants nanosystems drug permeability eye-related bioavailability in vitro and ex vivo corneal models HCE-T udc:615(043.3) BIOMEDICINE AND HEALTHCARE. Pharmacy. Pharmacy in vitro and ex vivo corneal models oftalmički ekscipijensi Farmakologija. Terapeutika. Toksikologija in vitro i ex vivo modeli rožnice permeabilnost bioraspoloživost drug permeability sense organs BIOMEDICINA I ZDRAVSTVO. Farmacija. Farmacija ophthalmic excipients Ophthalmic drugs Ophthalmic excipients Surfactants Nanosystems Drug permeability Eye-related bioavailability In vitro/ex vivo corneal models |
| Popis: | Bioavailability of topical ophthalmic products is substantially determined by the type and concentration of excipients. In addition to the use in conventional ophthalmic formulations, excipients are increasingly utilized in the development of innovative nanosystem-based ophthalmic formulations, in which excipients are supramolecularly organized into nano-sized structures, which can specifically interact with the anterior eye segment barriers and enhance the drug eyerelated bioavailability. Evaluation of the drug transcorneal permeability is a critical step in predicting eye-related bioavailability of topical ophthalmic drugs. In this thesis, the effect of unimers and supramolecular aggregates of the ophthalmic excipients on corneal barrier properties and ophthalmic drug permeability was evaluated, using in vitro (HCE-T cell-based) and/or ex vivo (excised porcine cornea) corneal models. Histological and functional characterization of the in vitro corneal model revealed variability of the HCE-T barrier phenotype, which highlights the important aspects to be considered in the further model development. HCE-T cell-based model of a specific histological structure, but showing improved barrier tightness and a very strong correlation of ophthalmic compounds permeability with excised porcine cornea, was shown to be suitable for the ophthalmic drug permeability evaluation considering the influence of ophthalmic excipients. Biopharmaceutical evaluation of melatonin-loaded nanosystems using HCE-T cell-based models revealed significant influence of chitosan on nanosystem biopharmaceutical properties. In lecithin/chitosan nanoparticles the presence of chitosan ensured mucoadhesive properties and prolonged melatonin release, controlling melatonin in vitro transcorneal permeation, which may provide enhanced melatonin eye-related bioavailability and therapeutic effect. The in vitro/ex vivo evaluation of the effect of nonionic surface active ophthalmic excipients on the ophthalmic drug permeability revealed their concentration-dependent permeability-decreasing effect, which was potentially related to the association of ophthalmic drugs with selfaggregates of surface active ophthalmic excipients. The results of this thesis provide valuable insight into the effect of ophthalmic excipients on ophthalmic drug transcorneal permeability, which may contribute to more directed and economical development of both conventional and innovative topical ophthalmic products. Bioraspoloživost topikalnih oftalmičkih pripravaka značajno je određena vrstom i udjelom eskcipijensa. Osim u konvencionalnim oftalmičkim oblicima, ekscipijensi primjenu pronalaze i u izradi inovativnih oftalmičkih oblika temeljenih na nanosustavima za dostavu lijeka. Interakcija ekscipijensa rezultira tvorbom supramolekulskih struktura nanodimenzija, koje mogu povećati bioraspoloživost lijeka u oku prevladavanjem barijera prednjeg segmenta oka. Ispitivanje permeabilnosti lijeka preko barijere rožnice ključan je korak u određivanju bioraspoloživosti topikalnih oftalmičkih lijekova. Cilj ovog doktorskog rada je bio ispitati utjecaj unimera i supramolekulskih agregata oftalmičkih ekscipijensa na barijerna svojstva rožnice i permeabilnost oftalmičkih lijekova korištenjem in vitro HCE-T modela epitela humane rožnice i ex vivo tkivnog modela rožnice svinje. Histološkom i funkcionalnom karakterizacijom in vitro modela utvrđena je određena varijabilnost fenotipa HCE-T barijere, što ukazuje na potrebu za dodatnom karakterizacijom čimbenika uzgoja s utjecajem na barijerna svojstva modela. HCE-T model specifične histološke strukture, ali čvršćih međustaničnih veza te vrlo dobre korelacije permeabilnosti oftalmičkih supstancija s ex vivo tkivnim modelom rožnice svinje, pokazao se prikladnim za ispitivanje učinka oftalmičkih ekscipijensa na permeabilnost oftalmičkih lijekova. Biofarmaceutskom karakterizacijom nanosustava za dostavu melatonina korištenjem in vitro HCE-T modela utvrđen je značajan utjecaj kitozana na biofarmaceutska svojstva nanočestica. U slučaju lecitinsko-kitozanskih nanočestica kitozan je osigurao mukoadhezivna svojstva, produljeno oslobađanje i kontroliranu permeaciju melatonina preko HCE-T barijere rožnice, što može pospješiti bioraspoloživost i terapijski učinak melatonina. U in vitro/ex vivo ispitivanjima uočeno je smanjenje permeabilnosti oftalmičkih lijekova ovisno o vrsti i koncentraciji neionskih površinski aktivnih oftalmičkih ekscipijensa, što je potencijalno uzrokovano interakcijom lijeka s agregatima površinski aktivnih oftalmičkih ekscipijensa. Rezultati ovog doktorskog rada značajan su doprinos razumijevanju učinka oftalmičkih ekscipijensa na permeabilnost oftalmičkih lijekova, što može pridonijeti usmjerenijem i ekonomičnijem razvoju konvencionalnih i inovativnih topikalnih oftalmičkih pripravaka. |
| Databáze: | OpenAIRE |
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